Lymphcytes of the Beta-cell lineage and their immunoglobulins (Ig) are an integral line of defense against foreign antigens but can also be deleterious agents in pathologic conditions such as chronic inflammatory disease and autoimmune disorders (e.g., rheumatoid arthritis, periodontitis, lupus). In order to therapeutically control desired or undesirable effects of B cells the ability to identify members of this heteregeneous population and an understanding of the events which regulate B cell development is crucial. Regulation of the more mature cells is known to depend in part upon Ig receptors exposed on these B cells. However the mechanisms which govern the development and activities of other B-lineage cells, not suspected of bearing surface-Ig, is largely conjectural; yet must be important during hematopoiesis in which the cells that populated the body are initially selected. I have evidence that immature bone marrow pre-B cells express Ig determinants which are detected by fowl antibodies to mouse-IG, but not by mammalian antisera. The purpose of this proposal is to examine the reactivity of the fowl antibodies and confirm whether or not the antigens recognized on bone marrow cells are Ig, or Ig-related molecules. Bone marrow cells will be isolated which either exhibit or lack membrane-Ig as detected by either flow or goat antisera and cells' membranes radiolabeled. Membrane antigen recovered from each cohort of cells by immuno-precipitation using each antiserum will be analyzed by polyacrylamide gel electrophoretic methods in order to determine structural features of the antigens. The physical properties of the molecules bound by fowl antibodies will be compared with those of classic Ig which are recognized by goat antiserum. Charge heterogeneity within a family of molecules will be considered a critical attribute indicative of relatedness to Ig. Cell-lines of known derivation and differentiation state, whom by nucleic acid studies to either be capable or incapble of producing Ig, will be similarly assayed and serve as controls verifying the classification of Molecules as Ig or unrelated antigens, respectively. If the fowl antibody is documened to react with Ig or related structures on B lineage cells previously regarded to lack Ig by serologic criteria it will not only signify a new understanding of B-lymphocyte biology but provide a new probe with which to identify and isolate these cells or their Igs for further investigation.